PARG inhibitors and method of use thereof
AssigneeCity of Hope
InventorsXiaochun Yu, Shih-Hsun Chen, Yate-Ching Yuan, Hongzhi Li, David Horne
Life of this patent
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Abstract
Provided herein are, inter alia, compounds inhibiting poly(ADP-ribose) Glycohydrolase (PARG) in a cancer cell and methods of treating cancer using compounds of the invention.
Claims11
A compound of formula (VIII):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1D is hydrogen or —CH3;
- R6 is hydrogen or —C(O)—OR6C;
- R7 is hydrogen or halogen;
- and
- R8 is —OR8D, —C(O)—OR8C, or unsubstituted C2-C4 alkyl;
- and
- R6C, R8C and R8D are independently hydrogen or —CH3.
A compound of formula (IX),
- or a pharmaceutically acceptable salt thereof, wherein:
- R1D, R2D, and R3D are independently hydrogen or unsubstituted C1-C4 alkyl;
- and
- R6 is hydrogen, halogen, —C(O)—OR6C, —OR6D, or unsubstituted C1-C4 alkyl;
- and
- R6C and R6D are independently hydrogen or —CH3.
A method of treating cancer in a subject suffering therefrom, the method comprising administering to the subject an effective amount of a compound having formula (VIII),
- or a pharmaceutically acceptable salt thereof,
- wherein:
- R1D is hydrogen or —CH3;
- R6 is hydrogen or —C(O)—OR6C;
- R7 is hydrogen or halogen;
- and
- R8 is —OR8D, —C(O)—OR8C, or unsubstituted C2-C4 alkyl;
- and
- R6C, R8C, and R8D are independently hydrogen or —CH3;
- wherein the cancer is selected from:
- breast cancer, ovarian cancer, lung cancer, pancreatic cancer, glioblastoma, uterine cancer, bladder cancer, esophagus cancer, gastric cancer, head and neck cancer, cholangiocarcinoma, mesothelioma, prostate cancer, colon carcinoma, fallopian tube cancer, lymphoma and leukemia.
A method of treating cancer in a subject suffering therefrom, the method comprising administering to the subject an effective amount of a compound having formula (IX):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1D, R2D, and R3D are independently hydrogen or unsubstituted C1-C4 alkyl;
- R6 is hydrogen, halogen, —C(O)—OR6C, —OR6D, or unsubstituted C1-C4 alkyl, and
- R6C and R6D are independently hydrogen or —CH3;
- wherein the cancer is selected from:
- breast cancer, ovarian cancer, lung cancer, pancreatic cancer, glioblastoma, uterine cancer, bladder cancer, esophagus cancer, gastric cancer, head and neck cancer, cholangiocarcinoma, mesothelioma, prostate cancer, colon carcinoma, fallopian tube cancer, lymphoma and leukemia.
A method of inhibiting a poly(ADP-ribose) glycohydrolase (PARG), the method comprising contacting the PARG with a compound having a formula (VIII) or (IX):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1D is hydrogen or —CH3;
- R6 is hydrogen or —C(O)—OR6C;
- R7 is hydrogen or halogen;
- R8 is —OR8D, —C(O)—OR8C, or unsubstituted C2-C4 alkyl;
- R6C, R8C, and R8D are independently hydrogen or —CH3;
- and
- R2D, and R3D are independently hydrogen or unsubstituted C1-C4 alkyl.
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound having formula (VIII) or (IX),
- or a pharmaceutically acceptable salt thereof, wherein:
- R1D is hydrogen or —CH3;
- R6 is hydrogen or —C(O)—OR6C;
- R7 is hydrogen or halogen;
- R8 is —OR8D, —C(O)—OR8C, or unsubstituted C2-C4 alkyl;
- R6C, R8C, and R8D are independently hydrogen or —CH3;
- and
- R2D, and R3D are independently hydrogen or unsubstituted C1-C4 alkyl.
Dependencies are inferred from the claim text.